Monomeric and dimeric complexes of pyrimidine-4,6-dicarboxylic acid with organometallic fac-[M(CO)3]+ (M = Re and 99mTc) core as radiopharmaceutical probes

Abstract

The current study describes the synthesis of monomeric and dimeric complexes of pyrimidine-4,6-dicarboxylic acid (H2pmdc) ligand with the organometallic fac-[M(CO)3]+ (M = Re and 99mTc) core which are the model for future design of imaging, therapeutic and theranostic radiopharmaceuticals. Monomeric complexes [M(CO)3(OH2)(Hpmdc)] (M = Re (1) and 99mTc (2)) were formed from the reaction of H2pmdc with [Re(CO)5Br] and [99mTc(CO)3(OH2)3]+ in aqueous solution respectively. The reaction of [Re(CO)5Br] with H2pmdc in ethanol (EtOH) led to the monomeric complex [Re(CO)3(OH2)(etpmdc)] (3), where etpmdc− is 6-(ethoxycarbonyl)pyrimidine-4-carboxylate anion which was formed from the mono-esterification of H2pmdc in parallel with its coordination to the fac-[Re(CO)3]+ unit. Dimeric complex (Et3NH)2[(µ-pmdc)2(Re(CO)3)2 (4) was obtained from the reaction of [Re(CO)5Br] with H2pmdc in water with addition of triethylamine (Et3N) as supporting base. The chemical identification of 1, 3 and 4 was achieved by using 1HNMR, 13CNMR, IR, ESI-MS and elemental analysis. Complex 3 was furtherly identified by using single crystal X-ray crystallography. The structural similarities of 1 and 2 was assessed by coinjection in the HPLC with UV/Vis detection coupled with a γ-detector followed by comparison of retention times of the γ-peak of 2 and the UV-peak of 1 which allowed unambiguous identification of 2. Heterodinuclear 99mTc/Re complex [(µ-pmdc)2(Re(CO)3)(99mTc(CO)3)2)]2− (5) was formed by reacting H2pmdc with [99mTc(CO)3(OH2)3]+ and [Re(CO)5Br] in aqueous solution. In parallel, the reaction also yielded complexes 1 and 2. The formation of 5 was assessed by injection in the HPLC with UV/Vis detection coupled with a γ-detector which displayed the radiochemical peak with the corresponding UV peak equivalent to that of the homologous non-radioactive complex 4.